Background: Acute respiratory distress syndrome (ARDS) is the leading cause of high mortality in intensive care units (ICUs) worldwide. An effective marker for prognosis in ARDS is particularly important given the absence of effective treatment strategies aside from small tidal volume ventilation. Previous studies identified an association between the neutrophil-to-lymphocyte ratio (NLR) and prognosis in critical patients. In this study, we explored the prognostic and predictive value of the NLR in ARDS patients. Methods: We retrospectively included 275 ARDS patients treated at a single institute from 2008 to 2015. After excluding patients with chronic lung disease, acute myocardial infarction and missing data, 247 patients were ultimately included in the analysis. Clinical characteristics and experimental test data, including the NLR, were collected from medical records at 24 hours after the ARDS diagnosis. Independent prognostic factors were determined by multivariate Cox regression analysis. Subgroup stratification was performed according to different factors, and the continuous factors were divided according to the median values. Results: The NLR in survivors was significantly lower than that in non-survivors (P14) and a low NLR group (NLR ≤14). We found that an NLR >14 was associated with a shorter overall survival (OS) (P=0.005). In the multivariate Cox regression model, we further identified an NLR >14 as an independent prognostic factor for OS [hazard ratio (HR) 1.532, (95% CI, 1.095–2.143), P=0.013]. Subgroup analysis showed that the prognostic value of the NLR was higher in hypertensive patients (P=0.009) and in patients with low red blood cell specific volume (P=0.013), high sodium (P=0.002) and high creatinine levels (P=0.017). Conclusions: The NLR is potentially a predictive prognostic biomarker in ARDS patients.

Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55–71) years old and 5 (4–6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35–56%). Proximal DVT was recognized in 9% (95% CI 3–15%) of the patients, while 46% (95% CI 35–56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06–0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38–3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03–1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.

Rationale: Demyelination is a major component of white matter injury, characterized by oligodendrocyte (OL) death and myelin sheath loss, which result in memory loss and cognitive impairment in the context of ischemic stroke. Accumulating evidence has shown that OLs can be generated by the direct activation of defined transcription factors (TFs) in human induced pluripotent stem cells (hiPSCs); however, the rapid acquisition of single TF-induced OL progenitor cells (OPCs) as cell therapy for ischemic stroke remains to be thoroughly explored.

Background: Toll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI. Methods: A case-control collection from Han Chinese of 298 healthy subjects, 278 sepsis-associated ALI and 288 sepsis alone patients were included. Three tag single nucleotide polymorphisms (SNPs) of the TIRAP gene and two additional SNPs that have previously showed association with susceptibility to other inflammatory diseases were genotyped by direct sequencing. The differences of allele, genotype and haplotype frequencies were evaluated between three groups. Results: The minor allele frequencies of both rs595209 and rs8177375 were significantly increased in ALI patients compared with both healthy subjects (odds ratio (OR) = 1.47, 95% confidence interval (CI):1.15-1.88, P = 0.0027 and OR = 1.97, 95% CI: (1.38-2.80), P = 0.0001, respectively) and sepsis alone patients (OR = 1.44, 95% CI: 1.12-1.85, P = 0.0041 and OR = 1.82, 95% CI: 1.28-2.57, P = 0.00079, respectively). Haplotype consisting of these two associated SNPs strengthened the association with ALI susceptibility. The frequency of haplotype AG (rs595209A, rs8177375G) in the ALI samples was significantly higher than that in the healthy control group (OR = 2.13, 95% CI: 1.46-3.09, P = 0.00006) and the sepsis alone group (OR = 2.24, 95% CI: 1.52-3.29, P = 0.00003). Carriers of the haplotype CA (rs595209C, rs8177375A) had a lower risk for ALI compared with healthy control group (OR = 0.69, 95% CI: 0.54-0.88, P = 0.0003) and sepsis alone group (OR = 0.71, 95% CI: 0.55-0.91, P = 0.0006). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. Conclusions: These results indicated that genetic variants in the TIRAP gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population. However, the association needs to be replicated in independent studies.

BackgroundSevere community-acquired pneumonia (SCAP) is one of the world's most common diseases and a major etiology of acute respiratory distress syndrome (ARDS). Cuproptosis is a novel form of regulated cell death that can occur in various diseases. MethodsOur study explored the degree of immune cell infiltration during the onset of severe CAP and identified potential biomarkers related to cuproptosis. Gene expression matrix was obtained from GEO database indexed GSE196399. Three machine learning algorithms were applied: The least absolute shrinkage and selection operator (LASSO), the random forest, and the support vector machine-recursive feature elimination (SVM-RFE). Immune cell infiltration was quantified by single-sample gene set enrichment analysis (ssGSEA) scoring. Nomogram was constructed to verify the applicability of using cuproptosis-related genes to predict the onset of severe CAP and its deterioration toward ARDS. ResultsNine cuproptosis-related genes were differentially expressed between the severe CAP group and the control group: ATP7B, DBT, DLAT, DLD, FDX1, GCSH, LIAS, LIPT1, and SLC31A1. All 13 cuproptosis-related genes were involved in immune cell infiltration. A three-gene diagnostic model was constructed to predict the onset of severe CAP: GCSH, DLD, and LIPT1. ConclusionOur study confirmed the involvement of the newly discovered cuproptosis-related genes in the progression of SCAP.

Pulmonary fibrosis (PF) is a disease characterized by dysregulated extracellular matrix deposition and aberrant fibroblast activation. Emerging evidence implicates that dysregulated copper metabolism contributed to fibrotic pathogenesis, yet its role and the therapeutic potential of copper modulation remain underexplored. This study investigated the involvement of cuproptosis, a programmed cell death induced by intracellular copper overload, in PF and evaluated the therapeutic efficacy of the copper chelator tetrathiomolybdate (TTM). In a bleomycin (BLM)-induced murine PF model, intratracheal BLM administration elevated lung copper levels, upregulated oligomerized DLAT, and exacerbated fibrosis, as evidenced by collagen deposition, α-smooth muscle actin, and transforming growth factor-beta expression. TTM treatment significantly attenuated fibrotic progression, reduced oxidative stress, and suppressed Olig-DLAT accumulation. In vitro, copper ionophores induced cuproptosis in bronchial epithelial cells, characterized by reduced viability, elevated intracellular Cu⁺, and Olig-DLAT aggregation, which were reversed by TTM. Furthermore, TTM mitigated TGF-β-driven epithelial–mesenchymal transition (EMT) and fibroblast-to-myofibroblast transition (FMT), downregulating collagen-1 and restoring E-cadherin expression. These findings establish cuproptosis as a novel mechanistic contributor to PF and highlight TTM’s dual role in restoring copper homeostasis and inhibiting fibrogenic pathways, offering a promising therapeutic strategy for fibrotic lung diseases.